Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

Chi, KN; Rathkopf, D; Smith, MR; Efstathiou, E; Attard, G; Olmos, D; Lee, JY; Small, EJ; Pereira de Santana Gomes, AJ; Roubaud, G; Saad, M; Zurawski, B; Sakalo, V; Mason, GE; Francis, P; Wang, G; Wu, D; Diorio, B; Lopez-Gitlitz, A; Sandhu, S; MAGNITUDE Principal Investigators

Author(s): Chi, KN; Rathkopf, D; Smith, MR; Efstathiou, E; Attard, G; Olmos, D; Lee, JY; Small, EJ; Pereira de Santana Gomes, AJ; Roubaud, G; Saad, M; Zurawski, B; Sakalo, V; Mason, GE; Francis, P; Wang, G; Wu, D; Diorio, B; Lopez-Gitlitz, A; Sandhu, S; MAGNITUDE Principal Investigators;
Details: Publication Year 2023-06-20,Volume 41,Issue #18,Page 3339-3351
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naive mCRPC when combined with androgen receptor signaling inhibition. METHODS: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort. RESULTS: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade >/= 3 adverse events. CONCLUSION: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP. [Media: see text].
Publisher: American Society of Clinical Oncology
Keywords: Male; Humans; *Abiraterone Acetate/adverse effects; *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics; BRCA1 Protein; BRCA2 Protein; Prednisone; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Department(s): Medical Oncology
PubMed ID: 36952634
Publisher's Version: https://doi.org/10.1200/JCO.22.01649
Open Access at Publisher's Site: https://doi.org/10.1200/jco.22.01649
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-09-12 07:43:58

Last Modified: 2023-09-12 07:44:44